Notice: Melanotan II is not approved as a medicinal product in any country. Bremelanotide (PT-141) is approved in the US as a prescription medicine (Vyleesi) but is not authorised in the European Union. This text is for information only and is based on published studies and information from regulatory authorities. Arion Bios products are intended exclusively for laboratory and research purposes. They are not medicines or dietary supplements and are not intended for use in humans or animals.

Melanotan II and PT-141 are often confused, and it is easy to see why. Both came out of the same research at the University of Arizona, share the same seven-amino-acid sequence and act on the same family of receptors. They differ by a single chemical group at the end of the chain.

Yet they ended up in very different places. PT-141, known scientifically as bremelanotide, went through large clinical trials and has been an approved medicine in the US since 2019. Melanotan II never got past small pilot studies, and authorities in several countries have warned against it. Below we compare the origin, structure, receptors, human studies and regulation of both substances. At the end, we explain how to tell them apart in a certificate of analysis.

The key differences at a glance

  • Structure: the same cyclic chain of seven amino acids. Melanotan II ends with an amide group (–NH2), PT-141 with a free acid (–OH).
  • Receptors: both substances activate several melanocortin receptors at once; PT-141 acts most strongly on MC1R and MC4R.
  • Original goal: Melanotan II was developed for sunless tanning, PT-141 for sexual function from the start.
  • Human evidence: Melanotan II has only small pilot studies from 1996–2000. PT-141 went through a phase 3 programme with more than 1,200 women.
  • Regulation: PT-141 is the US prescription medicine Vyleesi but is not authorised in the EU. Melanotan II is not approved anywhere.

A shared origin: from tanning to sexual function

The story of both substances begins with α-MSH, the hormone that triggers pigment production in the skin. From the 1980s, the team of Victor Hruby, Mac Hadley and Robert Dorr at the University of Arizona designed more stable synthetic versions of it. First came the linear Melanotan I (today the approved drug afamelanotide), and at the end of the 1980s the shorter, cyclic Melanotan II.

Melanotan II was originally meant to help people tan without the sun. But the very first pilot study in 1996, with three volunteers, produced an unexpected finding: alongside darker skin, the men experienced spontaneous erections. Research therefore turned to sexual function, and in 1998 a small blinded study showed erections in 8 of 10 men with psychogenic erectile dysfunction.

The US company Palatin Technologies built on this research. A 2006 review by Hadley and Dorr describes PT-141 as a new analogue of Melanotan II that the company was developing to treat sexual dysfunction in men and women. We cover the history of Melanotan II in more detail in Melanotan II: History, Mechanism and Research Explained.

The structures side by side

Both molecules are cyclic heptapeptides. They have the same seven amino acids and the same ring, formed by a bond between aspartic acid and lysine. They differ only in the final link: Melanotan II carries an amide group at the end, bremelanotide a free carboxylic acid. In the formula, this means one nitrogen and one hydrogen atom fewer and one oxygen atom more.

Parameter Melanotan II PT-141 (bremelanotide)
Sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH
End of the chain Amide (–NH2) Free acid (–OH)
Molecular formula C50H69N15O9 C50H68N14O10
Molecular weight 1024.2 g/mol 1025.2 g/mol
Monoisotopic mass 1023.54 Da 1024.52 Da
Receptors MC1R, MC3R, MC4R, MC5R MC1R, MC4R, MC3R, MC5R, MC2R (in descending order of potency)
Human studies Small pilot studies (1996–2000) Phases 1 to 3; 1,267 women in two phase 3 trials
Approved as a medicine Nowhere US since 2019 (Vyleesi), not in the EU

The formulas and masses come from the PubChem database; the data on bremelanotide also come from the US prescribing information for Vyleesi.

Receptors: why PT-141 is not “clean” either

There are five melanocortin receptors, and each controls something different. MC1R in the skin triggers dark pigment production; MC3R and MC4R in the brain are involved in energy balance, appetite and sexual function. MC2R in the adrenal glands responds to the hormone ACTH, and MC5R influences gland activity.

Melanotan II is a non-selective agonist: it activates MC1R, MC3R, MC4R and MC5R. Hence its broad range of effects, from pigmentation and reduced appetite to erections. Bremelanotide is often described as an MC4R-targeted substance. The US prescribing information for Vyleesi, however, states that bremelanotide activates the receptors non-selectively and acts most strongly on MC1R, followed by MC4R, MC3R, MC5R and MC2R.

This has practical consequences. The strong activity at MC1R explains why darkening of the skin and gums occurs even with the approved medicine. In the phase 3 trials, 1% of women had it. In another study in which the substance was given daily, pigmented patches appeared in 38% of participants and did not disappear in all of them after stopping. So the main difference between the two substances is not selectivity. It lies in how thoroughly they have been studied.

What human studies have shown

Melanotan II: small pilot studies

  • 1996: a pilot study with three healthy men (Life Sciences). Skin pigmentation increased, and spontaneous erections, stretching and yawning occurred.
  • 1998: a double-blind crossover study with 10 men with psychogenic erectile dysfunction (Journal of Urology). An erection occurred in 8 of 10 men. Transient nausea, stretching and yawning, and reduced appetite were more common than with placebo.
  • 2000: a study in men with erectile dysfunction and organic risk factors (Urology), with a similar result.

Melanotan II never went through large controlled phase 3 trials. Systematic data on its safety with long-term administration are therefore lacking.

PT-141: from nasal spray to approved medicine

Palatin first tested bremelanotide as a nasal spray in men with erectile dysfunction. A study published in 2004 showed that it induced erections statistically significantly more often than placebo in healthy men and in patients. In further, larger studies, however, nasal administration markedly raised blood pressure in some participants. The company therefore abandoned the nasal form in the late 2000s and switched to a subcutaneous injection.

At the same time, the focus shifted to women with hypoactive sexual desire disorder (HSDD). Two identically designed phase 3 trials called RECONNECT enrolled 1,267 premenopausal women and lasted 24 weeks. Compared with placebo, bremelanotide statistically significantly increased sexual desire and reduced the related distress. In absolute terms, the changes on the questionnaire scales were modest.

The US Food and Drug Administration (FDA) approved bremelanotide on 21 June 2019 under the name Vyleesi. It is intended for premenopausal women with acquired, generalised hypoactive sexual desire disorder that is not explained by another condition, relationship problems or the effects of medication. According to the prescribing information, the most common adverse reaction was nausea (40% versus 1.3% with placebo). The medicine also transiently raises blood pressure, by up to about 6 mmHg systolic, and slows the heart rate. Values usually return to baseline within 12 hours. We cover the clinical research on bremelanotide in more detail in PT-141: Mechanism of Action and Clinical Research.

Regulation

PT-141 (bremelanotide) has been a prescription medicine in the US since 2019. It is not authorised in the European Union. Outside pharmacies, it is sold as a research substance under the name PT-141.

Melanotan II is not approved as a medicine in any country. A 2017 review in the International Journal of Dermatology notes that health authorities in a number of countries have warned against the unregulated use of Melanotan I and II. The authors also summarise case reports of changes in moles and four described cases of melanoma that arose during or shortly after use. At the same time, they stress that a causal link has not been proven.

Both substances have an approved relative from the same family. Afamelanotide, the original Melanotan I, is authorised in the EU and the US for the rare disease erythropoietic protoporphyria. It shows that melanocortin research can produce an approved medicine when it goes through proper trials.

How to tell them apart in a certificate of analysis

Because the two substances differ only at the end of the chain, neither the name on the label nor HPLC purity is enough. HPLC shows the proportion of the main component, not its identity. What matters is mass spectrometry (MS):

  • The monoisotopic mass of Melanotan II is approximately 1023.5 Da, that of bremelanotide approximately 1024.5 Da. The difference is just under one dalton.
  • Peptides often appear in the spectrum as doubly charged ions [M+2H]2+. For Melanotan II this comes out at around m/z 512.8, for bremelanotide around m/z 513.3. The difference is therefore only about half a unit.

For these two substances, look in the certificate for a measured mass reported to at least one decimal place, not just a rounded figure. The instrument must also have sufficient resolution to separate the two peaks. We explain how to read a certificate in Peptide Certificate of Analysis: How to Read a CoA.

What Arion Peptides offers

Our range includes both substances as a lyophilised powder in a vial: PT-141 10 mg and Melanotan II 10 mg. Certificates of analysis for Arion Bios batches are available on the certificates of analysis page. The products are intended exclusively for laboratory and research purposes.

Frequently Asked Questions

Is PT-141 the same as Melanotan II?

No. They have the same seven-amino-acid sequence, but Melanotan II ends with an amide group and PT-141 with a free acid. They are two different molecules with different molecular weights.

Why does PT-141 also affect pigmentation?

Because it activates the melanocortin receptors non-selectively and acts most strongly on MC1R, which triggers pigment production in the skin. Darkening of the skin or gums is also listed in the prescribing information for the approved medicine Vyleesi.

Which one is approved as a medicine?

Only bremelanotide (PT-141), in the US under the name Vyleesi, for premenopausal women with acquired hypoactive sexual desire disorder. It is not authorised in the EU. Melanotan II is not approved anywhere.

Why did Melanotan II not go through clinical trials like PT-141?

The research was taken further by Palatin, which developed bremelanotide all the way to approval. Melanotan II remained at the stage of small pilot studies from 1996–2000.

How can I tell which substance a sample contains?

From the mass spectrometry result in the certificate of analysis. A monoisotopic mass of around 1023.5 Da corresponds to Melanotan II, around 1024.5 Da to bremelanotide. Because the difference is small, an accurate measurement is needed.

Summary

Melanotan II and PT-141 are the closest chemical pair you will find among research peptides: the same sequence, the same ring, and a difference in a single group at the end of the chain. Their fates diverged, however. Melanotan II remained at the pilot-study stage, and authorities warn against it. Bremelanotide went through a phase 3 programme and is an approved medicine in the US, albeit with nausea, a transient rise in blood pressure and skin darkening as known adverse effects.

For research, one thing follows above all: with such similar molecules, verified identity is key. The answer comes from a certificate of analysis with accurate mass spectrometry.

Sources

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  2. Wessells H, Fuciarelli K, Hansen J et al., “Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study”, Journal of Urology, 1998;160(2):389–393: pubmed.ncbi.nlm.nih.gov
  3. Hadley ME, Dorr RT, “Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization”, Peptides, 2006;27(4):921–930. DOI: 10.1016/j.peptides.2005.01.029
  4. Molinoff PB, Shadiack AM, Earle D et al., “PT-141: a melanocortin agonist for the treatment of sexual dysfunction”, Annals of the New York Academy of Sciences, 2003;994:96–102. DOI: 10.1111/j.1749-6632.2003.tb03167.x
  5. Diamond LE, Earle DC, Rosen RC et al., “Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction”, International Journal of Impotence Research, 2004;16(1):51–59. DOI: 10.1038/sj.ijir.3901139
  6. Kingsberg SA, Clayton AH, Portman D et al., “Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials”, Obstetrics & Gynecology, 2019;134(5):899–908. DOI: 10.1097/AOG.0000000000003500
  7. U.S. Food and Drug Administration, “VYLEESI (bremelanotide injection) – Prescribing Information”, 2019: accessdata.fda.gov
  8. Habbema L, Halk AB, Neumann M, Bergman W, “Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review”, International Journal of Dermatology, 2017;56(10):975–980. DOI: 10.1111/ijd.13585
  9. PubChem, “Melanotan II, CID 92432”: pubchem.ncbi.nlm.nih.gov
  10. PubChem, “Bremelanotide, CID 9941379”: pubchem.ncbi.nlm.nih.gov
  11. EMA, “Scenesse (afamelanotide), EPAR”: ema.europa.eu